Figure 7. Mechanisms of the Shh pathway-induced cell motility and invasiveness.

The binding of Shh to the 12-pass transmembrane receptor Ptch leads to the translocation and activation of Smo, a G protein-coupled receptor. Smo activates Gli1 through inhibiting SUFU, an inhibitors of Gli1. In addition, Smo activation also leads to the formation of the G_β and G_γ heterodimer, which activates the PI-3-kinase pathway. AKT activation leads to cytoskeleton remodeling and cell motility. Snail expression can be transcriptionally induced by Gli1. The Shh pathway may also contribute to increased invasiveness by converting cells to cancer stem-like cell phenotype and c-Met activation.